On December 2, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported positive final results from the randomized Phase 2 study of its lead oncology drug, CM24, a humanized monoclonal antibody that blocks CEACAM1, in patients with pancreatic ductal adenocarcinoma (PDAC) (Press release, Purple Biotech, DEC 2, 2024, View Source [SID1234648722]).

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"We are very excited about the final data, demonstrating CM24’s clear and consistent improvement across all efficacy endpoints evaluated in our randomized Phase 2 study," stated Purple Biotech CEO Gil Efron. "The enhanced results in patients with CEACAM1 and other serum markers gives us further optimism that a biomarker enriched patient population selection could further strengthen CM24’s magnitude of efficacy, potentially positioning CM24 as a treatment for multiple CEACAM1-expressing malignancies in line with its mechanism of action."

Michael Cecchini, MD Associate Professor of Medicine at the Yale Cancer Center, a principal investigator in this study, commented, "The promising results in PDAC, along with the identification of a potential patient subgroup that may benefit from targeting CEACAM1 and NET serum levels, potentially position CM24 as an encouraging treatment option. As a clinician, it is inspiring to see data that suggest the potential for improved outcomes in patients with late-stage metastatic PDAC, who desperately need new and effective therapies. These findings support further investigation of CM24 in combination with a checkpoint inhibitor and standard-of-care chemotherapy to improve outcomes not only in PDAC but also in other challenging cancer types."

Summary of Data and Findings:

The Phase 2 study evaluated CM24, a novel first-in-class multi-functional anti-CEACAM1 antibody, in combination with Bristol Myers Squibb’s immune checkpoint inhibitor nivolumab plus stand-of-care (SoC) chemotherapy in second-line metastatic PDAC patients versus SoC chemotherapy alone. CM24 is a humanized monoclonal antibody that blocks CEACAM1, a multi-faceted membrane glycoprotein that is one of the main proteins present on NETs, also acting as a pro-angiogenic and anti-apoptotic agent collectively promoting tumor invasiveness, metastasis and immune evasion.

The primary endpoint of the study is OS and the secondary endpoints include PFS, ORR and disease control rate (DCR). A Bayesian methodology was used to estimate the magnitude of effect of the experimental arm versus the SoC arm in each chemotherapy cohort; the study was not powered for hypothesis testing. A total of 63 patients were enrolled, across 18 centers in the U.S., Spain, and Israel in 2 parallel and independent randomized study cohorts (total of 2 arms per cohort). The experimental arms administered patients with CM24 plus nivolumab and a choice of one of two SoC chemotherapies for second-line PDAC, dependent on prior first line therapy regimen; either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil (5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV), while the control arms administered either respective chemotherapy alone. CA19-9 as well as additional exploratory biomarkers were also evaluated. Of the 63 patients enrolled, 32 were in the gemcitabine/nab-paclitaxel study (experimental and control) and 31 were in the Nal-IRI/5FU/LV study (experimental and control). The gemcitabine/nab-paclitaxel-based part of the study was impacted by informative censoring of the control arm that led to an imbalance between the control and experimental arms, rendering this part of the study unsuitable for analysis; this part of the study has no impact on the CM24+nivolumab+Nal-IRI/5FU/LV portion of the study.

The study’s final efficacy results in the Nal-IRI/5FU/LV intent to treat (ITT) cohort population are summarized in the following table:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 16) Nal/IRI/5FU/LV Arm
(n = 15)
Hazard ratio for OS 0.81 (95% CI: 0.38-1.71)
Median OS 7.92 months 5.55 months
6 months OS rate 53 % 47 %

Hazard Ratio for PFS 0.75 (95% CI: 0.35-1.61)
Median PFS 3.9 months 2.0 months
3 months PFS rate 67 % 47 %
6 months PFS rate 17 % 13 %
ORR 25 % 7 %
DCR 63 % 47 %

A consistent and continuous decrease of CA19-9, a clinically validated PDAC biomarker, was observed in the experimental arm reaching a median percentage reduction from baseline of approximately 80% vs. an increase of 40% in the control arm.

Subgroup analysis of patients with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 4)
Nal/IRI/5FU/LV Arm
(n = 7)

Hazard ratio for OS 0.21 (95% CI: 0.04-1.06)
Median OS 9 months 3.9 months
Hazard ratio for PFS <0.1 (95% CI: 0-inf)
Median PFS 4.7 months 1.8 months
ORR 50 % 0 %
DCR 100 % 43 %

An additional subgroup analysis of patients, which comprised 80% of the patients in the study cohort, with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL together with patients with pretreatment serum Myeloperoxidase (MPO) levels of 200 ng/mL and 600 ng/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 13) Nal/IRI/5FU/LV Arm
(n = 11)
Hazard ratio for OS 0.39 (95% CI: 0.16-0.98)
Median OS 7.90 months 5.50 months
Hazard ratio for PFS 0.28 (95% CI: 0.11-0.73)
Median PFS 4.1 months 1.9 months
ORR 31 % 0 %
DCR 69 % 36 %

Additional biomarkers analysis based on the patient pretreatment biopsies, demonstrated significant OS and PFS benefit (HR 0.1, P=0.013 and HR 0.19, P=0.033, respectively) in patients with both high tumor CEACAM1 (≥100) and low Combined Positive Score (CPS) (≤1) (a measure of PD-L1 positive tumor cells) supporting the CM24/nivolumab combined treatment and its mechanistic rationale, and may open a new opportunity for patients who are not eligible for anti-PD1 therapy in various indications

The CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated, with the most frequent treatment emergent Grade 3 or higher adverse events being diarrhea (4 patients in the experimental arm vs. 1 patient in the control arm), fatigue (2 patients in the experimental arm vs. no patients in the control) and neutropenia (2 patients in the experimental arm vs. no patients in the control). Accordingly, no meaningful difference in safety and tolerability were observed between the experimental arm and SoC arm.

"The significant results in the subgroup based on certain range of serum CEACAM1 and MPO levels, that covered 80% of the patients in the Nal-IRI cohort, is encouraging. We believe that tumors with low CEACAM1 or NETs are less reliant on these targets whereas extremely high levels may suggest potential resistance to the treatment. Based on the emerging role of neutrophil extracellular traps (NETs) in cancer and the positive findings of our study in this selected population overlapping with CEACAM1 expression, we are planning a 3-arm Phase 2b study comparing either CM24 plus a PD1 inhibitor or CM24 monotherapy to SoC in multiple tumor types selected based on their NET and CEACAM1 expressions. This design will also investigate the contribution of parts in regard to the need for PD1 blockade on top of CM24. We plan to target patients with higher serum levels of CEACAM1 and MPO, as they are potentially more likely to benefit from CM24 treatment," stated Dr Michael Schickler, Head of Clinical and Regulatory Affairs.

On December 2, 2024 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported a new clinical trial collaboration and supply agreement with Novartis in frontline metastatic breast cancer (Press release, Olema Oncology, DEC 2, 2024, View Source [SID1234648721]). Olema has also entered into a securities purchase agreement for the private placement of approximately $250.0 million of common stock and pre-funded warrants to purchase common stock with new and existing institutional and accredited investors (the "Private Placement").

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"We are now fully enabled to initiate our planned pivotal Phase 3 clinical trial, OPERA-02, for palazestrant in combination with ribociclib in frontline ER+/HER2- metastatic breast cancer. Our new agreement with Novartis, which includes sufficient ribociclib drug supply for the planned approximately 1,000 patient trial, is a major milestone. When combined with our Private Placement of $250.0 million of common stock and pre-funded warrants with high-quality, long-term investors, Olema now expects to have the necessary resources to execute OPERA-02, the Phase 1/2 study of OP-3136, and the ongoing Phase 3 OPERA-01 monotherapy trial," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "We remain on track to share topline data from OPERA-01 in 2026 and we are excited to present our latest data from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) next week."

New Clinical Trial Collaboration and Supply Agreement Enables Phase 3 OPERA-02 Trial

Under the terms of the agreement, Novartis will provide Olema with ribociclib drug supply for the planned, Olema-sponsored, Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in ER+/HER2- frontline advanced or metastatic breast cancer. All clinical data and inventions from the trial will be jointly owned while Olema maintains global commercial and marketing rights to palazestrant.

Private Placement Funds Expanded Clinical Development Activities

The Private Placement is expected to close on or about December 4, 2024, subject to the satisfaction of customary closing conditions. The financing included participation by new and existing investors Adage Capital Partners LP, Bain Capital Life Sciences, BVF Partners L.P., Driehaus Capital Management, Janus Henderson Investors, Paradigm BioCapital Advisors, Wellington Management, Woodline Partners LP, and a large investment manager. Pursuant to the terms of the securities purchase agreement, Olema will issue 19,928,875 shares of common stock at a purchase price of $9.08 per share and pre-funded warrants to purchase up to an aggregate of 7,604,163 shares of common stock at a purchase price of $9.0799 per pre-funded warrant, for gross proceeds of approximately $250.0 million, before deducting placement agent fees and other offering expenses. The pre-funded warrants will have an exercise price of $0.0001 per share of common stock, be immediately exercisable and remain exercisable until exercised in full. The Private Placement is being conducted in accordance with applicable Nasdaq rules and was priced using the average Nasdaq official closing price of Olema’s common stock for the five trading days ended November 27, 2024.

Jefferies is acting as lead placement agent with J.P. Morgan, Citigroup, Goldman Sachs & Co. LLC, LifeSci Capital, Oppenheimer & Co., and H.C. Wainwright & Co. acting as placement agents in the Private Placement.

Olema intends to use the net proceeds from the Private Placement, together with its current cash, cash equivalents and marketable securities, to fund the OPERA-02 trial, the Phase 1/2 study of OP-3136, and its ongoing Phase 3 OPERA-01 monotherapy trial of palazestrant, and for working capital and general corporate purposes.

The securities described above have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state’s securities laws, and are being issued and sold pursuant to an exemption from registration provided for under the Securities Act. Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Olema has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued and sold in the Private Placement. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

About Palazestrant (OP-1250)

Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In preclinical studies, palazestrant completely blocks ER-driven transcriptional activity in both ESR1 wild-type and mutant forms of breast cancer. In Olema’s ongoing clinical trials for advanced or metastatic ER+/HER2- breast cancer, palazestrant has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus).

On December 2, 2024 Lixte Biotechnology Holdings, Inc. (the "Company") reported to have amended a Development Collaboration Agreement (the "Collaboration Agreement") with the Netherlands Cancer Institute, Amsterdam (NKI), one of the world’s leading comprehensive cancer centers, and Oncode Institute, Utrecht, a major independent cancer research center, to identify the most promising drugs to be combined with LB-100, and potentially LB-100 analogues, to be used to treat a range of cancers, as well as to identify the specific molecular mechanisms underlying the identified combinations (Filing, 8-K, Lixte Biotechnology, DEC 2, 2024, View Source [SID1234648720]).

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On November 29, 2024, the parties signed an amendment ("Amendment 3") to the Collaboration Agreement. This Amendment provides for a pause in the ongoing study activities and any payments thereunder until the initiation of a Phase 1b clinical trial combining LB-100 with a WEE1 inhibitor in metastatic colorectal cancer patients. The collaboration will resume upon dosing of the first patient in this clinical trial (the "Effective Date"), with the termination date revised to be one (1) year from the dosing date of the first patient.

Under Amendment 3, the parties will seek to study translational data derived from patient samples in clinical trials at NKI. Amendment 3 provides for a reduced annual budget of €100,000, invoiced quarterly, for one year from the Effective Date as compered to the initial budget of €250,000. The foregoing description of Amendment 3 does not purport to be complete and is subject to and qualified in its entirety by the full text of Amendment 3, a copy of which is filed hereto as Exhibit 10.1.

On December 2, 2024 Kura Oncology, Inc. (NASDAQ: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that it will be hosting a virtual investor event at 8:00 a.m. ET / 5:00 a.m. PT on Monday, December 9, 2024, to discuss the KOMET-007 combination trial of the Company’s oral and selective menin inhibitor, ziftomenib, following the presentation of updated clinical data at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, Kura Oncology, DEC 2, 2024, View Source [SID1234648719]).

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The virtual event will feature members of the management team along with investigators from the KOMET-007 trial. The live call may be accessed by dialing (800) 715-9871 for domestic callers and (646) 307-1963 for international callers and entering the conference ID: 4326549. A live webcast will be available here and in the Investors section of Kura’s website, with an archived replay available shortly after the event.

On December 2, 2024 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported positive updated interim clinical data for its JANX007 clinical program. Janux will host a virtual event today at 4:30 PM ET (Press release, Janux Therapeutics, DEC 2, 2024, View Source [SID1234648718]).

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"These clinical data show substantial activity with JANX007 in 5L metastatic castration-resistant prostate cancer patients and provide compelling support for the doses we’ve selected for expansion trials directed at pre-PLUVICTO 2L and 3L patients," said David Campbell, Ph.D., President and CEO, Janux Therapeutics. "We look forward to rapidly advancing JANX007 into second and third-line therapy where a substantial unmet need remains and where we believe JANX007’s highly differentiated profile could allow for broad usage, if approved. This is an exciting day for Janux, but more importantly the prostate cancer patients we serve."

Updated interim, clinical data for PSMA-TRACTr JANX007 in mCRPC as of November 15, 2024

JANX007 is in a Phase 1a clinical trial in patients with advanced or metastatic prostate cancer (mCRPC). The patients enrolled in the trial were heavily pre-treated with a median of four prior lines of therapy. As of the November 15, 2024 data cutoff, 16 pre-PLUVICTO patients have been treated once-weekly at a target dose ranging from 2 mg to 9 mg in the Phase 1a clinical trial. High prostate-specific antigen (PSA) response rates and deep PSA declines were observed across all doses; 100% of patients achieved best PSA50 declines, 63% of patients achieved best PSA90 declines, and 31% of patients achieved best PSA99 declines. Durability of PSA declines at a target dose ≥ 2 mg were observed; 75% of patients maintained PSA50 declines at ≥ 12 weeks and 50% of patients maintained PSA90 declines at ≥ 12 weeks. Deep and durable PSA responses were observed irrespective of resistance driver aberration status, or prior treatments with a taxane or ARPi. In RECIST-evaluable patients, anti-tumor activity was observed with confirmed and unconfirmed partial responses in 50% (4/8) of patients.

JANX007 was well-tolerated with cytokine release syndrome (CRS) and CRS-related adverse events primarily limited to cycle 1 and grades 1 and 2. Similarly, treatment-related adverse events (TRAEs) not associated with CRS were primarily limited to cycle 1 and grades 1 and 2. The maximum tolerable dose for JANX007 has not yet been reached.

Based on these efficacy and safety results, two once-weekly step dose regimens have been identified for Phase 1b expansion trials directed at pre-PLUVICTO 2L and 3L patients. Janux anticipates providing another update on JANX007 in 2025.

Webcast Information

Janux will host a live webcast today at 4:30 PM ET. A live question and answer session will follow the formal presentation. To register for the event, please click here.

Participant Dial-In Details

USA & Canada: (800) 715-9871

International: 1 (646) 307-1963

Conference ID: 2229349

To access the live webcast, please visit the Investors section of the Company’s website. A replay of the webcast presentation will be available on the Company’s website at View Source for at least 30 days.